In vivo evaluation of the safety of triptolide-loaded hydrogel-thickened microemulsion.
Triptolide (TP) is a major active component of Tripterygium wilfordii Hook F (TWHF), which is used to treat rheumatoid arthritis (RA). TP has a narrow therapeutic window. To increase the therapeutic index of TP, a novel TP-loaded transdermal delivery system, named TP-loaded hydrogel-thickened microemulsion (TP-MTH), has been developed to treat RA. Our previous studies have demonstrated the good efficacy of TP-MTH in animals. This paper evaluated the safety of TP-MTH with several animals. Results demonstrated no obvious toxicities in a series of toxicity tests: acute toxicity study of TP-MTH (1.2mg/kg) in rabbits, 6-month long-term toxicity study of TP-MTH (0.06, 0.18, 0.54mg/kg) in rabbits, safety pharmacology study of TP-MTH (0.03, 0.09, 0.27mg/kg, for 5 d) in mice and beagle dogs, skin irritation study in rabbits, and skin allergic reaction test in guinea pigs. Only mild reversible skin irritation signs were observed on the skin of animals. These studies suggest that topical TP-MTH is a promising drug formulation for the treatment of RA.
Xu
Lingyun
L
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China.
Pan
Jinyuan
J
Chen
Qiyou
Q
Yu
Qizhi
Q
Chen
Huabing
H
Xu
Huibi
H
Qiu
Yinsheng
Y
Yang
Xiangliang
X
D000279:Administration, Cutaneous; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D004285:Dogs; D004342:Drug Hypersensitivity / Q000473:pathology; D004655:Emulsions; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D006168:Guinea Pigs; D020100:Hydrogels; D007202:Indicators and Reagents; D007509:Irritants / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D012867:Skin / Q000473:pathology; D014018:Tissue Distribution
D018501:Antirheumatic Agents; D004224:Diterpenes; D004655:Emulsions; D004852:Epoxy Compounds; D020100:Hydrogels; D007202:Indicators and Reagents; D007509:Irritants; D010616:Phenanthrenes; C001899:triptolide